| Version | Summary | Created by | Modification | Content Size | Created at | Operation |
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| 1 | Sammer Ul Hassan | + 3937 word(s) | 3937 | 2021-03-12 07:09:39 | | | |
| 2 | Vivi Li | Meta information modification | 3937 | 2021-03-23 08:36:07 | | |
The spectrum of emerging new diseases as well as re-emerging old diseases is broadening as infectious agents evolve, adapt, and spread at enormous speeds in response to changing ecosystems. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent phenomenon and may take a while to understand its transmission routes from less travelled territories, ranging from fomite exposure routes to wastewater transmission. The critical challenge is how to negotiate with such catastrophic pandemics in high-income countries (HICs ~20% of the global population) and low-and middle-income countries (LMICs ~ 80% of the global population) with a total global population size of approximately eight billion, where practical mass testing and tracing is only a remote possibility, particularly in low-and middle-income countries (LMICs). Keeping in mind the population distribution disparities of high-income countries (HICs) and LMICs and urbanisation trends over recent years, traditional wastewater-based surveillance such as that used to combat polio may help in addressing this challenge. The COVID-19 era differs from any previous pandemics or global health challenges in the sense that there is a great deal of curiosity within the global community to find out everything about this virus, ranging from diagnostics, potential vaccines/therapeutics, and possible routes of transmission. In this regard, the fact that the gut is the common niche for both poliovirus and SARS-CoV-2, and due to the shedding of the virus through faecal material into sewerage systems, the need for long-term wastewater surveillance and developing early warning systems for better preparedness at local and global levels is increasingly apparent.
The emergence of the COVID-19 pandemic, caused by a novel coronavirus (SARS-CoV-2), requires extraordinary measures to deal with this global challenge. There are various factors that have contributed to its far-ranging spread, including enhanced human-to-human transmissibility, sanitation and hygiene, ecological modifications, microbiological adaptation, human susceptibility to infection, human demographics and behaviour, international trade & travel, poverty and social inequality, inadequate public health measures, climate change, and population density (number of individuals/sq km) [1][2][3][4]. Coronaviruses are classified into four genera (alpha, beta, gamma, delta), each one with multiple species with SARS-CoV being divided into different strains [5]. They constantly circulate in humans, and out of the seven known members of the group, four endemic human coronaviruses (HCoV-229E, -NL63, -OC43, and -HKU1) cause mild respiratory, enteric, hepatic, and neurological diseases [6]. In contrast, two relatively recent epidemic strains, severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV) caused severe respiratory disease or pneumonia [7][8][9][10][11]. The SARS-CoV-1 outbreak of 2002–2003 was the first small-scale human pandemic wake-up call of the 21st century, with a mortality rate of approximately 10%, climbing to about 50% in the elderly population; this rate is higher than many other viral diseases [12].
With this background, COVID-19 caused by a seventh member of the coronavirus group (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has emerged as a threat to global human health & the economy due to its widespread human-to-human transmission [13] Therefore, understanding SARS-CoV-2′s environmental niches and ecological adaptation for its transmission through the aerial route (coughing & sneezing), exhaled air in the hospital or community settings in association with asymptomatic carriers [14] and exposure through fomites [15][16] to hospital wastewater [17][18], or sewers could be considered as a risk factor in gauging future risk assessment and developing epidemiological models [19]. SARS-CoV-2 can persist in various environments as well as on different surfaces [20]. For example, it is viable on stainless steel or plastic surfaces for 48–72 h until reduction occurs [15]. Moreover, the virus persists for 4–5 days on glass, PV, silicon rubber, and surgical gloves [21][22]. Copper surfaces are known to damage the virus [15]. Additionally, high temperatures (70 °C) interferes with viral persistence while resists low temperatures (22 °C) for 14 days [23][24][25]. The viral persistence seems not to be statistically influenced at different pH values [25]. A higher humidity rate enhances viral persistence [25]. SARS CoV-2 (with variable average mortality rates ranging from <1 to >10%), like SARS-CoV-1 of 2003 (with a mortality rate of approximately 10%) and MERS-CoV of 2012 (with a mortality rate of approximately 35–40%), are transmitted by air or direct contact, but their transmission through water has not been thoroughly explored and investigated [26][27][28][29]. However, transmission through wastewater has been better elucidated for another member of the group, human enteric coronavirus (HCoV-OC43), which is associated with necrotizing enterocolitis and gastroenteritis [9][30][31]. SARS-CoV-2 discharged from faecal (102 up to 108 RNA copies per gram which can be secreted for 14–21 days) [18][32] and urine specimens have been successfully cultured in Vero E6 cells [33][34] and the release of the virulent virus into the gastrointestinal tract indicates the potential faecal-oral transmission path [35], which needs further investigation in order for it to be established beyond doubt [18][32][34][36].
COVID-19 was declared a public health emergency of international concern by WHO based on the International Health Regulation (2005) in April 2020, and the need for coordinated efforts for a better response was stressed [37]. The COVID-19 emergency not only reminds us of the 1918 Spanish-flu pandemic but also, to some extent, another ongoing global crisis, polio, a crippling human disease caused by wastewater dwelling ancient poliovirus, which may have originated as early as 1580 BC [38]. SARS-CoV-2 appears to persist for a long time, like influenza and poliovirus, and hence, multipronged approaches are required to deal with this pandemic in order to prevent it from rapidly transitioning to become endemic globally. Moreover, more widespread epidemics and new waves are expected in the near future, widening the gap between rich and poor [39]. In order to avoid catastrophic outcomes and to deal with the current pandemic and subsequent epidemics, the global community should enhance massive testing capacity in order to make it affordable for all [40][41].
However, considering the ongoing spread of SARS-CoV-2, there is a dual challenge of tracking it not only in terms of its community transmission but also monitoring its global outreach and penetrance [40][42]. It may not be eliminated from the environment or human ecosystem due to its potential future endemicity [43]. In light of this, the challenge may be addressed not only through effective surveillance strategies but also by implementing the outcomes of intelligent data generation approaches for better preparedness and response [44][45][46]. Large-scale and quick population screening with the higher sensitivity and specificity is key to detecting the community transmission of SARS-CoV-2 [47][48][49]. Hence, it is vital to develop cost-effective, portable, fast testing protocols using a small number of reagents and to employ them to tackle the COVID-19 international global health emergency [50][51][52]. Economic surveillance approaches with broader applications will help to assess the risk of community transmission better and consequently help in implementing subsequent measures by testing, tracking, and isolation, not only to reduce the burden on healthcare systems or hospitals but also to make quick decisions to prevent the spread of localised community transmission of SARS-CoV-2.
Similarly, forthcoming third waves, as well as repeated local outbreaks, in the absence of mass-scale testing or limited capacity for clinical testing, can be predicted by wastewater surveillance by improving existing epidemiological models, addressing various variables such as temperature, humidity, matrix composition, and rainfall [18][53][54][55]. Under the current circumstance, this environmental surveillance could be implemented in wastewater treatment plants as a tool designed to help authorities to coordinate the exit strategy to lift their coronavirus lockdowns gradually. In this regard, risk assessment for detecting viruses from infected/contaminated sites by developing and implementing rapid diagnostic methodologies for point-of-care detection for long-term surveillance is a key challenge.
Based on the SARS-CoV-2 transmission patterns, WHO issued guidelines on physical distance (2 m) and wearing masks, initially by symptomatic patients and later by all in public places, and by implementing lockdowns [56][57][58]. There has been confusion due to insufficient knowledge on virus transmission, which has undoubtedly led to indecisive and ineffective mitigation strategies and policies triggering the propagation of the COVID-19 pandemic [59][60]. Long-term, inexpensive surveillance of SARS-CoV-2 would help public health agencies to implement appropriate measures and governments to shape their economies, and the key to that is employing cost-effective and non-invasive surveillance strategies [61]. Environmental microbiologists have investigated pathogens such as waterborne, foodborne and faecal-oral viruses or enteric viruses such as norovirus, hepatitis A virus, and poliovirus from the sewage excreted through faeces and used it as a public health surveillance tool [62][63][64][65][66][67][68][69][70], and more recently for monitoring SARS-CoV-2 [71][72][73][74][75][76][77][78][79][80].
SARS-CoV-2 can resist standard disinfection treatments such as sodium hypochlorite and at an eco-friendly reduced concentration of free chlorine [81][82][83]. This is reflected by high levels of SARS-CoV-2 (0.05–1.87 × 104/L present in wastewater even after treatment with sodium hypochlorite, perhaps due to the virus being embedded in faecal particles [84] or in association with other resistant microbes [85]. This may lead to leakage of the virus and its spread through drainage pipelines on a larger scale [84]. Moreover, the hitchhiking of non-enveloped and enveloped viruses along with the coexistence of a relatively resistant plethora of microbes or bacteria (e.g., Escherichia coli and f2 phage) may help their better survival by aiding them to tolerate chemicals or disinfectants such as lipid solvents, chloroform and to tolerate a relatively broad range of pH and temperature [34][86][87][88].
It is unprecedented in history that global economies and communities have so extensively relied on the availability of cost-effective rapid, and reliable testing methods, as they are for SARS-CoV-2; such a response allows governments to devise timely intelligent strategies for effective responses. This rigorous contact tracing helped countries like Taiwan, Singapore, and South Korea to avoid lockdowns [89]. Global economies can only recover up to their full potential when all the economic and industrial growth sectors and the masses are convinced that the risk of transmission of SARS-CoV-2 has been marginalised, or at least, we know with precision where it is circulating [90][91][92]. In this regard, the economies which are predominantly relying on selected lockdowns and relaxing them without any concrete data will result in even bigger surges impacting both economies and public health [93].
Environmental or wastewater monitoring is an effective tool for passive mass screening or surveillance generating useful data for early warning against pathogens such as SARS-CoV-2 [61][94][95]. Studies have just begun to investigate the environmental factors controlling the distribution and abundance of SARS-CoV-2 [96][97][98]. However, the importance of this linkage is well understood in the context of poliovirus. SARS-CoV-2 has been reported in many studies to be circulating in medical wastewater [84], septic tanks [84], and wastewater [73], in a situation similar to diarrhoea-causing HCoVA-OC43 [9][84]. Wastewater surveillance can facilitate properly timed and targeted shutdowns and reopening in specific densely populated geographic areas that lack, in particular, means and resources [99][100]. This can be facilitated by using viral concentration methods for wastewater samples in order to increase the sensitivity of the generally used tests [101][102]. These methods include ultracentrifugation, the use of electropositive and electronegative membranes, and polyethylene glycol precipitation [103][101][102][104][105].
There is an urgent need to perform cost-effective epidemiological surveillance studies [106][107]. Although massive RT-qPCR testing campaigns are being launched in several countries to monitor the actual prevalence of SARS-CoV-2, this is not a practical surveillance approach for the general population over the long term [106]. Several studies have reported that coronaviruses had been involved in nosocomial outbreaks with environmental contamination as a possible route of transmission; these include a recent study that found nosocomial transmission of SARS-CoV-2 [108]. Nevertheless, the extent of environmental contamination and the mode of transmission are still largely unknown. In a recent study, a patient suffering from upper respiratory tract infection without clinical signs of pneumonia had two positive stool samples for SARS-CoV-2 on RT-PCR despite not having diarrhoea, indicating that viral shedding in the stool could be a possible transmission route [109].
Therefore, it is important to gather information about the presence and future destiny of SARS-CoV-2 in sewage to assess the possible risk to sewage workers and the population at large, and to assess if sewage surveillance is a suitably sensitive tool for monitoring SARS-CoV-2 in the community. In Spain (city of Valencia), a team of scientists and engineers are accessing the sewage network in an attempt to find out where COVID-19 outbreaks are likely to spring up next [110]. Several studies found that sewage surveillance may act as an early alarm for the emergence of COVID-19 in communities, similar to the poliovirus sewage surveillance, which has been used for this goal [111][74]. Most studies, which are performed to assess the presence of SARS-CoV-2 in sewage, are based on detection of the virus by making RT-qPCR or nested RT-PCR, after specific treatment of sewerage samples [112][71][73][106]. Furthermore, Randazzo et al. [106] consistently detected SARS-CoV-2 RNA in samples taken when communicated cases in that region were only incipient. They also found that the wastewater viral RNA context remarkably increased and suggested the subsequent ascent in the number of declared cases. They strongly suggested that SARS-CoV-2 was undergoing community transmission earlier than previously believed, indicating that wastewater analysis is a cost-effective and sensitive tool for COVID-19 epidemiological surveillance.
Medema et al. [74] reported the first detection of SARS-CoV-2 in sewage in the Netherlands. Although they found that COVID-19 prevalence was low, the detection of the SARS-CoV-2 in sewage indicates that sewage surveillance could be a sensitive tool in monitoring the circulation of the virus in the population. In France, Wurtzer et al. [71] proposed that quantification of SARS-CoV-2 genomes in wastewater should be in agreement with the number of non-symptomatic or symptomatic carriers. They also aimed to study the impact of lockdown on the SARS-CoV-2 in wastewaters, so their study was performed from 5 March to 23 April 2020, thus including the period of lockdown in France (from 17 March 2020). They confirmed that the rise in the genome units in raw wastewater perfectly followed the rise in human COVID-19 cases seen at the regional level. SARS-CoV-2 genomes could be detected before the beginning of the exponential growth of the epidemic [71]. They detected a noticeable decrease in the quantities of genomes units simultaneously with the low number of new COVID-19 cases which was an expected outcome of the lockdown. They suggested that quantitative monitoring of SARS-CoV-2 genomes in wastewater should give further and pivotal information for better surveillance of SARS-CoV-2 circulation at the local or regional scale. In Pakistan, Sharif et al. [80] found that 21 wastewater samples (27%) from 13 districts were PCR positive, indicating that wastewater surveillance has an epidemiologic potential which could be considered to be an early warning system for monitoring viral tracking in different districts.
Haramoto et al., [113] carried out the first environmental surveillance for SARS-CoV-2 RNA in Japan. They detected SARS-CoV-2 RNA (2.4 × 103 copies/L) in secondary-treated wastewater. Samples collected from influent and river water were negative for SARS-CoV-2 RNA. The remarkable information is that SARS-CoV-2 RNA was detected when the reported community cases were high, implying that SARS-CoV-2 wastewater surveillance may be considered as an ideal surrogate for community cases. Therefore, it is important to have information about the presence and future destiny of SARS-CoV-2 in sewage to assess the possible risk to sewage workers and the population at large, and to assess if sewage surveillance is considered to be a sensitive tool for monitoring SARS-CoV-2 in the community.
According to the recent estimate, about 4/5th of the global population (~8 billion) live in developing economies, and 54% of that population resides in an urban area and this figure will likely exceed 66% by 2030 [114]. The urbanisation trends in LMICs, in particular Africa and South Asia, where the healthcare systems are fragile, are faster and the concomitant [115] associated with the increasing population density per square kilometre provides a perfect environment for the broad spread of infectious diseases like SARS-CoV-2. Therefore, the urban environment, which has already become the most complex human habitat, along with the current SARS-CoV-2 pandemic, means that COVID-19 disease management will require extraordinary measures from an environmental and public health perspective as an international health emergency on a global scale.
It is envisioned that the recent paradigm shift in our understanding will ensue with the routine testing of wastewater treatment facilities, for the emerging viral disease COVID-19, as an early warning system and will help public health departments in informed decision-making. The credibility of the surveillance can be gauged by the improved sensitivity of the tests where a single introduction of infection could be detected in a wastewater reservoir from a community [116][117]. Therefore, testing wastewater regularly, not only for the presence or absence of SARS-CoV-2, but also to determine the viral load or amount of corresponding genetic material will be able to give insight about hotspots for days or weeks for COVID-19. The wastewater surveillance data generated will certainly give public health teams and hospital management breathing space for better preparedness and educated responses, and government can reinforce strict social distancing measures by imposing smart lockdowns. Moreover, the pooled information retrieved regarding the health status of the community, in particular for viruses such as polio and SARS-CoV-2, can thereafter reinforce prioritisation of vaccination and, if necessary, testing, tracing, and isolation in identified hotspot zones vis a vis the ongoing SARS-CoV-2 pandemic. As a matter of fact, one of the better ways to undertake surveillance, in particular in those countries where testing capacity has not been matching the population size, is to simulate or predict the transmission patterns, and infection rate through regular wastewater surveillance [61]. For example, the wastewater-based monitoring system for polio has been in place since 1989 as an early warning system against pathogen reintroduction, and it helped, for instance, in 2013, in better preparedness and launching a subsequent educational response at hotspots in Israel through vaccination of a vulnerable population [118][119][120]. There are only limited numbers of countries or coalitions which have reported SARS-CoV-2 RNA in wastewater and developed a well-planned WBE programme for COVID-19, mainly Australia, Canada, and Europe [74][121][122][123] with limited implementation in the USA [124].
In addition to the increasing interest of the global scientific community in the fields of epidemiology, diagnostics, and clinical medicine for COVID-19 in the last six months or so, the interest in WBE as a non-invasive early warning predictor or monitoring tool for infectious diseases, including SARS-CoV-2, has already tremendously increased and will further increase in the near future [71][72][111][73][74][70][125][126][127][128][129][130]. It will help to minimise the risk of relaxing restrictions or lockdowns too soon or help in imposing intelligent small lockdowns. This is supported by the recent Italian study where WBE was successfully employed to investigate the spatial and temporal patterns of viral spread among the population [70].
In order to avoid a catastrophic outcome and to deal with the current pandemic and subsequent epidemics, the global community not only should enhance massive testing capacity so that it is affordable for all (~1 USD/test) but should also be thinking of scaling up the vaccine supply to meet the demands of billions of doses (~8 billion) as soon as it is available. Vaccines are considered to be the ultimate panacea against SARS-CoV-2 where some vaccines have already developed and others still at various stages of development. On the contrary, relying entirely on herd immunity may well be very costly as, in order for this to be effective in any country, the majority of the population, 70% to 90%, has to be naturally exposed to SARS-CoV-2 and recover or build immunity or it must be achieved through vaccination which became available for some types of vaccines. Therefore, in the process of building heard immunity on such a large scale, there will be fatal consequences for a vulnerable population (old age or with underlying conditions) within the global community as has been seen in countries like Sweden and in the crippling of healthcare systems. The operational scale of such a huge supply chain can be gauged from the fact that in 2018, approximately 116.3 million infants were immunised globally for polio (DPT) [131], whereas one billion doses are produced and used annually. It is highly likely that widening gaps of significant proportions for the population not vaccinated for SARS-CoV-2 will create a huge disparity with the result that COVID-19 epidemics will hit many countries around the globe hard and impact the central dogma of One health, hence influencing the global economy (One-Health ⇔ One-Economy). This has been shown, for instance, by economic modelling, visualising a polio-free world with the gain of at least USD 40–50 billion predominantly in LMICs in addition to mitigating the deadly consequences of terrible lifelong disease [132].
It is believed that monitoring of water resources, including wastewater, reveals the presence of a broad array of pathogenic microorganisms including PV, SARS-CoV-1 and SARS-CoV-2 [116][133][88], which may be introduced by faecal shedding, freshwater runoff from sewers, rivers, and streams [127][134]. Therefore, PV and SARS-CoV-2 are certainly linked not only with personal sanitation & hygiene but also with the overall human health ecosystem as well as the environmental ecosystem. In addition, both PV and SARS-CoV-2 are single-stranded, positive-sense RNA genomes, and both can exist either symptomatically, with a similar incubation period, and also circulate asymptomatically or silently within-population [116][135], heavily relying on human behaviours. In order to better develop epidemiological models of disease spread in diverse environments, such as those prevailing in HICs and LMICs, it will be essential to trace the circulation of SARS-CoV-2 mostly in wastewater, in particular in hotspots, along the lines of polio environmental surveillance campaigns that have been carried out in the past [118][136].
The COVID-19 pandemic has clearly shown that the global population is highly vulnerable to SARS-CoV-2, which is amplified by environmental drivers. Its transition from pandemic to epidemic to endemic can only be gauged, managed, and understood by probing the environment, especially wastewater. The examination of high-risk groups and composite human faecal samples using environmental surveillance has helped in determining high-risk groups or pockets for polio, and hence such supplementary surveillance is mandatory for maintaining polio-free status [136]. A similar approach should be adopted for SARS-CoV-2 along with enhanced efforts not only to improve campaign quality, penetrating to remote and difficult-to-access areas, but also to screen in the most populous areas. Wastewater surveillance or WBE has become more relevant in particular for LIMCs and highly dense populations in urban settings where testing and tracing for SARS-CoV-2 is either economically not feasible [61] or not possible because of lack of depth in their diagnostic (testing-tracing) capacity. For such low-income settings, poverty-stricken regions or hotspots, WBE can help to assess the disease burden and support timely implementation of mitigation strategies and help LMICs, in particular, to avoid the worst of economic recession by easing lockdowns based on real data and restoring livelihoods for marginalised global communities.
The emergence of COVID-19 has exposed not only global healthcare systems but also their preparedness to deal with the challenges of infectious diseases. Indeed, understanding the epidemiology of disease & corresponding population behaviour in a highly polarised world, i.e., high-income countries (HICs) & low & middle-income countries (LMICs), will help us to understand the transmission conundrum of such once a millennium virus in future. The interdisciplinary approaches will certainly be at the forefront to help nations better prepare for assessing the current pandemic risk or dealing with the third wave or surges of COVID-19 as we move further. Multipronged approaches will be required, ranging from preparedness and national action plans to developing and implementing technologies for surveillance. A microfluidic chip technique integrated with geographic information for real-time surveillance of SARS-CoV-2 in wastewater channels to assess the risk by developing epidemiological models will be of significant value. Large-scale and quick population screening with greater sensitivity and specificity is key to detecting community transmission of SARS-CoV-2. Hence, it is vital to develop cost-effective portable, fast testing protocols using a small number of reagents and for these to be employed for the COVID-19 international global health emergency. Microfluidic cassettes manipulating small amounts of fluids using the channel at the micron-level not only offer broader applications in diagnostics and environmental surveillance but are also cost-effective, portable, rapid, and simple to use. The innovative, refined approaches can further speed up the development and availability of SARS-CoV-2 wastewater diagnostics by modifying conventional clinical laboratory benchtop tests, and hence, help to deal with the COVID-19 emergency with better information content.